crossing96/oncoscreening huggingface dataset:
The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells.	OBJECTIVE: To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. METHODS: We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. RESULTS: MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. CONCLUSIONS: These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa.	bladder
Prospective evaluation of health-related quality of life after radical cystectomy: focus on peri- and postoperative complications.	OBJECTIVES: To analyse the impact of perioperative complications and complex treatment courses on postoperative health-related quality of life (HRQOL) after radical cystectomy (RC) and continent (ONB) or incontinent (IC) urinary diversion at multiple prospective time points. METHODS: A total of 121 consecutive patients underwent RC with curative intent between 2013 and 2014. HRQOL was prospectively assessed preoperatively, after 3 and 12 months, using the QLQ-C30 questionnaire. The impact of complex perioperative treatment courses including cases requiring surgical re-interventions was retrospectively assessed using Martin criteria and the Clavien-Dindo scale. Urinary continence was determined using the validated ICIQ-SF questionnaire. Statistical analysis included Kruskal-Wallis ANOVA, Spearman's rank correlation, and ordinal regression models (p < 0.05). RESULTS: A total of 100 patients underwent further analysis. Physical functioning (PF), role functioning (RF), and global health status (GHS) scores were higher in the ONB subgroup both preoperatively (p < 0.001, 0.010, 0.048) and 3 months after RC (p = 0.003, 0.048, 0.019). Clavien complications ≥III led to reduced PF levels after 3 months (p = 0.050) without effect on GHS (p = 0.825). Operating time and length of critical care monitoring correlated with 3 months pain scores in the ONB subgroup (p = 0.003, 0.009) without affecting GHS (p = 0.603, 0.653). Continent urinary diversion was an independent predictor of increased HRQOL after 3 months (p = 0.021), however, not after 12 months (p = 0.803). CONCLUSIONS: Patients receiving an IC have lower PF, RF, and GHS scores than those receiving ONB. Perioperative complications and complicated treatment courses can affect HRQOL subdomains but do not significantly impact the GHS. ONB is an independent predictor for better overall HRQOL 3 months, but not 12 months after RC.	bladder
Role of coagulation factors in urological malignancy: A prospective, controlled study on prostate, renal and bladder cancer.	OBJECTIVES: To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. METHODS: This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal (n = 44), prostate (n = 56) and bladder cancer (n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. RESULTS: Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). CONCLUSIONS: The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events.	bladder
Venous thromboembolism in metastatic urothelial carcinoma or variant histologies: incidence, associative factors, and effect on survival.	Venous thromboembolism (VTE) is common in cancer patients. However, little is known about VTE risk in metastatic urothelial carcinoma or variant histologies (UC/VH). We sought to characterize the incidence, associative factors, including whether various chemotherapy regimens portend different risk, and impact of VTE on survival in metastatic UC/VH patients. Patients diagnosed with metastatic UC/VH from 2000 to 2013 were included in this multicenter retrospective, international study from 29 academic institutions. Cumulative and 6-month VTE incidence rates were determined. The association of first-line chemotherapy (divided into six groups) and other baseline characteristics on VTE were analyzed. Each chemotherapy treatment group and statistically significant baseline clinical characteristics were assessed in a multivariate, competing-risk regression model. VTE patients were matched to non-VTE patients to determine the impact of VTE on overall survival. In all, 1762 patients were eligible for analysis. There were 144 (8.2%) and 90 (5.1%) events cumulative and within the first 6 months, respectively. VTE rates based on chemotherapy group demonstrated no statistical difference when gemcitabine/cisplatin was used as the comparator. Non-urotheilal histology (SHR: 2.67; 95% CI: 1.72-4.16, P < 0.001), moderate to severe renal dysfunction (SHR: 2.12; 95% CI: 1.26-3.59, P = 0.005), and cardiovascular disease (CVD) or CVD risk factors (SHR: 2.27; 95% CI: 1.49-3.45, P = 0.001) were associated with increased VTE rates. Overall survival was worse in patients with VTE (median 6.0 m vs. 10.2 m, P < 0.001). Thus, in metastatic UC/VH patients, VTE is common and has a negative impact on survival. We identified multiple associated potential risk factors, although different chemotherapy regimens did not alter risk.	bladder
T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer.	Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.	bladder
Lycium barbarum polysaccharides inhibit proliferation and migration of bladder cancer cell lines BIU87 by suppressing Pi3K/AKT pathway.	The aim of this study was to verify whether Lycium barbarum polysaccharides inhibits proliferation and migration of BIU87 cells through Pi3K/AKT pathway. Different concentrations of Lycium barbarum polysaccharides were used to incubate with BIU87cells. LY-294002 and IGF-1 were used to inhibit and activate Pi3K/AKT pathway respectively. MTT were used to investigate the proliferation of BIU87cells. Transwell chambers and wound healing were used to test the migratory ability of BIU87cells. Western blotting were used to investigate the expressions of P21,P27,MMP-2, MMP-9, AKT and p-AKT in BIU87cells. Compared with the control group, the proliferation and migration of BIU87cells and the expression of p-AKT were significantly decreased in the study group; the inhibitory effect of the downregulation of p-AKT by LY-294002on the induction of BIU87cells proliferation and migration was identical to that of Lycium barbarum polysaccharides; upregulation of p-AKT by IGF-1 reversed the Lycium barbarum polysaccharides-induced inhibition of BIU87cells dedifferentiation. In conclusion, LBP inhibits the proliferation and migration of BIU87 cells by suppressing Pi3K/AKT signaling pathway.	bladder
Development, validation and clinical application of Pelvic Lymphadenectomy Assessment and Completion Evaluation: intraoperative assessment of lymph node dissection after robot-assisted radical cystectomy for bladder cancer.	OBJECTIVES: To develop a scoring tool, Pelvic Lymphadenectomy Appropriateness and Completion Evaluation (PLACE), to assess the intraoperative completeness and appropriateness of pelvic lymph node dissection (PLND) following robot-assisted radical cystectomy (RARC). PATIENTS, SUBJECTS AND METHODS: A panel of 11 open and robotic surgeons developed the content and structure of PLACE. The PLND template was divided into three zones. In all, 21 de-identified videos of bilateral robot-assisted PLNDs were assessed by the 11 experts using PLACE to determine inter-rater reliability. Lymph node (LN) clearance was defined as the proportion of cleared LNs from all PLACE zones. We investigated the correlation between LN clearance and LN count. Then, we compared the LN count of 18 prospective PLNDs using PLACE with our retrospective series performed using the extended template (No PLACE). RESULTS: A significant reliability was achieved for all PLACE zones among the 11 raters for the 21 bilateral PLND videos. The median (interquartile range) for LN clearance was 468 (431-545). There was a significant positive correlation between LN clearance and LN count (R(2) = 0.70, P < 0.01). The PLACE group yielded similar LN counts when compared to the No PLACE group. CONCLUSIONS: Pelvic Lymphadenectomy Appropriateness and Completion Evaluation is a structured intraoperative scoring system that can be used intraoperatively to measure and quantify PLND for quality control and to facilitate training during RARC.	bladder
Cautious use and optimal dose of morphine for relieving malignant pain in a complex patient with multiple comorbidities.	Oral morphine remains the drug of choice for the management of severe pain due to cancer as per WHO ladder of analgesia. Providing adequate pain relief in palliative care settings for pain due to cancer is challenging. Options become limited in cases of associated systemic comorbidities such as renal dysfunction, hypoproteinaemia, anaemia. Patients with renal dysfunction and other comorbidities may develop drug overdose due to abnormal pharmacokinetics. Renal dysfunction affects the pharmacokinetics of morphine by altering its absorption, metabolism and clearance. Plasma albumin also influences drug availability, its plasma distribution and thus available free morphine for its clinical effect. Morphine should be used cautiously for the treatment of pain in patients with renal failure, hypoproteinaemia, hyperbilirubinaemia and anaemia. In such patients, alternate opiates like fentanyl, hydromorphone, or oxycodone may be used as these drugs are not significantly excreted by the kidneys.	bladder
α(v)β(3)-Isoform specific erbium complexes highly specific for bladder cancer imaging and photodynamic therapy.	We have synthesized a bifunctional erbium-porphyrin tumor imaging and PDT agent (Er-R3) that is capable of killing bladder cancer cells via its selective binding to the integrin α(v)β(3) isoform overexpressed on the cell membrane.	bladder
Radical cystectomy: do we need standardization?	The first series of radical cystectomy with a definition of surgical landmarks was published in 1949 and was characterized by a high perioperative mortality and a 5-year survival rate around 50%. Decades later, nevertheless many surgical progresses were made and the perioperative mortality dropped to 2,5%, this had not lead to an improvement of long term survival rates, also because a standardization of the procedure is still missing. Areas covered: Radical cystectomy is performed with different surgical techniques obmitting a standardization. The comparability of many studies is therefore difficult or havely compromised. A paragon with other diciplines was made emphazing that there high surgical quality is defined, measured and controlled. A systematic literature search was made selecting finally 76 article adressing this issue. Expert commentary: Surgical guidelines in uro-oncology are vague and a definition of surgical quality is missing. A view outside of the box could be very helpful. This is a plea for a change.	bladder
Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation.	Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids. The captured glycoproteins were subsequently detected using the same validated antibodies as in RPPA. We demonstrated the outstanding specificity, sensitivity, and quantitative capabilities of polyGPA by capturing and detecting purified as well as endogenous α-1-acid glycoprotein (AGP) in human plasma. We further applied quantitative N-glycoproteomics and the strategy to validate a panel of glycoproteins identified as potential biomarkers for bladder cancer by analyzing urine glycoproteins from bladder cancer patients or matched healthy individuals.	bladder
Occupational risk factors for relapse-free survival in bladder cancer patients.	The influence of occupational risk factors on bladder cancer development is well investigated. However, studies on the influence on bladder cancer prognosis are rare. Therefore, it was of interest to investigate the time to first relapse in the follow-ups of three case-control series from Dortmund, Neuss, and Lutherstadt Wittenberg, Germany. Relapse-free survival of in total 794 urinary bladder cancer patients (Dortmund 174, Neuss 407, Lutherstadt Wittenberg 213) was derived from medical records. Cox regression models were used to determine the impact of profession and exposure to bladder carcinogens if the risk factor was present in at least four cases. One or several relapses were observed in 416 cases (52%). Median time to first relapse was 0.94 yr. Ten professions were observed in at least 4 patients. No significant associations were found. However, workers in the leather industry (n = 4), printing industry (n = 4), transportation (n = 43), and chemical industry (n = 40) and locksmiths/mechanics (n = 44) showed shorter relapse-free times. No trend to shorter relapse-free time was observed for miners (n = 42), agriculturists (n = 18), painters/lacquerers (n = 21), colorant production and processing workers (n = 7), foundry workers (n = 5), and persons exposed to aromatic amines (n = 45). Although the follow-up comprised nearly 800 cases, data on occupations and exposures of interest were not sufficient to obtain significant results. However, first results indicated potential associations that are worth further investigations.	bladder
Rb knockdown accelerates bladder cancer progression through E2F3 activation.	Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high. Rb knockdown enhanced bladder tumor cell proliferation and migration, aggravated with p53 silence. Interestingly, Rb silence results in E2F3, Myc and mTOR signaling pathway activation, contributing to bladder cancer cell proliferation and apoptosis suppression mainly through caspase-3 inhibition in vitro and in vivo. Immunohistochemical analysis revealed that Rb is highly expressed in normal bladder cells, but was repressed in tumor tissues of the bladder completely, suggesting a possible role of Rb as a tumor suppressor.	bladder
[Bladder Metastasis of Renal Cell Carcinoma 7 Years after Ex Vivo Partial Nephrectomy and Auto-Transplantation : A Case Report].	Metastasis of renal cell carcinoma (RCC) to urinary bladder is extremely rare. We report a case of metastasis arising from RCC to the urinary bladder 7 years after treatment of bilateral RCC. A 74-year-old man was diagnosed with bilateral multiple renal tumors (T1aN0M1, PUL, OSS) with two lesions in the right kidney and a solitary lesion of the left kidney in 2008. He underwent laparoscopic radical nephrectomy for the right side in September 2008. The next month, ex vivo partial nephrectomy and auto-transplantation was performed for the left kidney because the tumor was located very close to the collecting system. Metastatectomies for the lung and bone followed and the histopathological findings of all lesions were clear cell carcinoma. The following years went well without any recurrence. Seven years after the surgery, the patient complained of asymptomatic gross hematuria and cystoscopy revealed a solitary non-papillary tumor of the bladder. Transurethral resection of the tumor was performed in June 2015 and the histopathological diagnosis of the resected specimens was clear cell carcinoma. Because the additional immunohistochemical examinations were positive for CD10 and negative for CK7, we diagnosed the bladder tumor as metastasis arising from RCC. Direct dissemination of the tumor cells into the urinary tract during partial nephrectomy followed by implantation to the bladder mucosa is a probable mechanism of metastasis in this case.	bladder
MiR-193b Mediates CEBPD-Induced Cisplatin Sensitization Through Targeting ETS1 and Cyclin D1 in Human Urothelial Carcinoma Cells.	Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) plays multiple roles in tumor progression. Studies have demonstrated that cisplatin (CDDP) induced CEBPD expression and had led to chemotherapeutic drug resistance. However, the underlying molecular mechanisms of CDDP-regulated CEBPD expression and its relevant roles in CDDP responses remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Abnormal miRNAs expression is associated with tumor progression. In current study, a large-scale PCR-based miRNA screening was performed to identify CEBPD-associated miRNAs in urothelial carcinoma cell line NTUB1. Eleven miRNAs were selected with more than twofold changes. MiR-193b-3p, a known tumor suppressor, down-regulated proto-oncogenes Cyclin D1, and ETS1 expression and led to cell cycle arrest, cell invasion, and migration inhibition. The expression of miR-193b-3p was associated with the DNA binding ability of CEBPD in CDDP response. CEBPD knocking-down approach provided a strong evidence of the positive correlation between CEBPD and miR-193b-3p. CDDP-induced CEBPD trans-activated miR-193b-3p expression and it directly targeted the 3'-UTR of Cyclin D1 and ETS1 mRNA, and silenced the protein expression. In addition, miR-193b-3p also inhibited cell migration activity, arrested cell at G1 phase, and sensitized NTUB1 to CDDP treatment. In conclusion, this study indicates that CEBPD exhibits an anti-tumorigenic function through transcriptionally activating miR-193b-3p expression upon CDDP treatment. This study provides a new direction for managing human urothelial carcinoma. J. Cell. Biochem. 118: 1563-1573, 2017. © 2016 Wiley Periodicals, Inc.	bladder